Rubis Blazej, Paszel Anna, Kaczmarek Mariusz, Rudzinska Magdalena, Jelen Henryk, Rybczynska Maria
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Przybyszewskiego 49 St, 60-355 Poznan, Poland.
Br J Nutr. 2008 Dec;100(6):1183-91. doi: 10.1017/S0007114508981423. Epub 2008 Apr 29.
So far, a protective influence of phytosterols on the human organism and atherogenesis has been suggested. Most studies have concentrated on the cytotoxic efficacy of phytosterols on cancer cells. However, there are only a few reports showing their influence on normal cells. The aim of the present study was to determine whether dietary plant sterols and their thermal processing products could influence the viability of normal, abdominal endothelial cells that play a crucial role in atherogenesis. Thus, we studied the effect of rapeseed oil-extract components, beta-sitosterol, cholesterol and their epoxy-derivatives, 5 alpha,6 alpha-epoxy-beta-sitosterol and 5 alpha,6 alpha-epoxycholesterol, on the proliferation and viability of human abdominal aorta endothelial cells HAAE-2 in vitro. We showed strong cytotoxic properties of beta-sitosterol in HAAE-2 cells (half maximal inhibitory concentration (IC50) = 1.99 (SEM 0.56) microm) and, interestingly, a weaker cytotoxic effect of 5 alpha,6 alpha-epoxy-beta-sitosterol (IC50>200 microm). Moreover, we observed a significantly stronger cytotoxic activity of beta-sitosterol than cholesterol (IC50 = 8.99 (SEM 2.74) microm). We also revealed that beta-sitosterol as well as cholesterol caused apoptosis, inducing caspase-3 activity in the cells (60 % increase compared with control cells) that corresponded to the DNA fragmentation analysis in a terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) study. Although absorption of plant sterols is low compared with cholesterol, they can still influence other physiological functions. Since they effectively reduce serum LDL-cholesterol and atherosclerotic risk but also decrease the viability of cancer cells as well as normal cells in a time- and dose-dependent manner in vitro, their influence on other metabolic processes remains to be elucidated.
到目前为止，已经有人提出植物甾醇对人体和动脉粥样硬化形成具有保护作用。大多数研究都集中在植物甾醇对癌细胞的细胞毒性作用上。然而，仅有少数报告显示了它们对正常细胞的影响。本研究的目的是确定膳食植物甾醇及其热加工产物是否会影响在动脉粥样硬化形成中起关键作用的正常腹部内皮细胞的活力。因此，我们研究了菜籽油提取物成分、β-谷甾醇、胆固醇及其环氧衍生物5α,6α-环氧-β-谷甾醇和5α,6α-环氧胆固醇对人腹主动脉内皮细胞HAAE-2体外增殖和活力的影响。我们发现β-谷甾醇对HAAE-2细胞具有很强的细胞毒性（半数最大抑制浓度（IC50）= 1.99（标准误0.56）μm），有趣的是，5α,6α-环氧-β-谷甾醇的细胞毒性作用较弱（IC50>200μm）。此外，我们观察到β-谷甾醇的细胞毒性活性明显强于胆固醇（IC50 = 8.99（标准误2.74）μm）。我们还发现β-谷甾醇以及胆固醇会导致细胞凋亡，诱导细胞中的半胱天冬酶-3活性（与对照细胞相比增加60%），这与末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）研究中的DNA片段化分析结果一致。尽管与胆固醇相比，植物甾醇的吸收率较低，但它们仍然可以影响其他生理功能。由于它们能有效降低血清低密度脂蛋白胆固醇和动脉粥样硬化风险，但在体外也会以时间和剂量依赖的方式降低癌细胞以及正常细胞的活力，因此它们对其他代谢过程的影响仍有待阐明。
